The cell membrane is well recognized as a primary target for the pathological action of both disease processes and environmental pollutants and the overall objective of this project is to evaluate the role of selective membrane permeability and transport in the overall function of epithelial cell tissues. Combined physiological and morphological techniques, such as auto-radiography and isolation of cell membranes, are being employed to investigate basic mechanisms of epithelial cell transport using several lower vertebrate models; A. Regarding the role of the ouabain sensitive, Na,K-ATPase powered, sodium pump in specialized salt secreting epithelia, we have localized the pump to the basal-lateral membrane in both chloride cells of the teleost gill and tubule cells of the elasmobranch rectal gland. Using the same technique, 3H-ouabain autoradiography, the sodium pump was also localized to the basal-lateral membrane in a more conventional salt absorbing epithelium, teleost urinary bladder. As an aid to solving the enigma of basal-lateral pumps transporting salt in both directions, i.e., secretory as well as absorptive, a flat opecular skin preparation with a high chloride cell density has just been developed. B. Regarding individual transport steps for phenol red-like acids, we have demonstrated that exaggerated urinary concentration, i.e., 1000 times plasma, occurs in intact flounder as well as isolated renal tubules with chlorphenol red, PAH, and Diodrast and that the acidic DDT metabolite, DDA is handled by at least the peritubular membrane transport step. Even more important, we are in the process of identifying the first example of a carrier-mediated brush-border step for organic acids with the aid of purified membrane vesicles prepared from flounder kidney cells.